Tachyphlaxis to phentolanune-induced hypotensive effect in rats

Phentolamine-induced tachyphylaxis in rats was investigated. The ED_(50) of the fall in blood pressure iv phentolamine increased to 110+-41 #mu#g/kg from 41+-9 #mu#g/kg and the E_(max) decreased to 4.5+-1.9 kPa from 6.8+-1.3 kPa when tachyphylaxis was reached in anesthetized rats. A decreasing trend in sensitivity to phentolamine was derived as the drug was iv administered repeated to conscious rats. A cross tachyphylaxis occurred to phentolamine and prazosin, but not to sodium nitroprusside, nifedipine or hexamethonium bromide. The #alpha#-adrenergic receptors in the anococcygeal muscle of the phentolamine tachyphylactic rats exhibited low pD_(2) to noradrenaline and low pA_(2) to phentolamine. These results support the concept that alpha receptors may play a major role in the process leading to an induced tachyphylaxis to phentolamine.